3CCD

1.0 A Structure of Post-Succinimide His15Asp HPr

3CCD の概要

• エントリーDOI: 10.2210/pdb3ccd/pdb
• 関連するPDBエントリー: 1CM2
• 分子名称: Phosphocarrier protein HPr, SULFATE ION (3 entities in total)
• 機能のキーワード: succinimide, isoaspartate, protein damage, autophosphatase, transferase
• 由来する生物種: Escherichia coli
• 細胞内の位置: Cytoplasm: P0AA04
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 18406.64

構造登録者

Napper, S.,Prasad, L.,Delbaere, L.T.J. (登録日: 2008-02-25, 公開日: 2008-10-21, 最終更新日: 2023-08-30)

主引用文献

Napper, S.,Prasad, L.,Delbaere, L.T.
Structural investigation of a phosphorylation-catalyzed, isoaspartate-free, protein succinimide: crystallographic structure of post-succinimide His15Asp histidine-containing protein
Biochemistry, 47:9486-9496, 2008

PubMed Abstract: Aspartates and asparagines can spontaneously cyclize with neighboring main-chain amides to form succinimides. These succinimides hydrolyze to a mixture of isoaspartate and aspartate products. Phosphorylation of aspartates is a common mechanism of protein regulation and increases the propensity for succinimide formation. Although typically regarded as a form of protein damage, we hypothesize succinimides could represent an effective mechanism of phosphoaspartate autophosphatase activity, provided hydrolysis is limited to aspartate products. We previously reported the serendipitous creation of a protein, His15Asp histidine-containing protein (HPr), which undergoes phosphorylation-catalyzed formation of a succinimide whose hydrolysis is seemingly exclusive for aspartate formation. Here, through the high-resolution structure of postsuccinimide His15Asp HPr, we confirm the absence of isoaspartate residues and propose mechanisms for phosphorylation-catalyzed succinimide formation and its directed hydrolysis to aspartate. His15Asp HPr represents the first characterized protein example of an isoaspartate-free succinimide and lends credence to the hypothesis that intramolecular cyclization could represent a physiological mechanism of autophosphatase activity. Furthermore, this indicates that current strategies for succinimide evaluation, based on isoaspartate detection, underestimate the frequencies of these reactions. This is considerably significant for evaluation of protein stability and integrity.

PubMed: 18702519
DOI: 10.1021/bi800847a

実験手法

X-RAY DIFFRACTION (1 Å)